Women and Epilepsy

There are a number of important factors to consider with regard to epilepsy and the female gender. These factors include hormonal regulation & menstruation, conception and contraception, sexual function, influence of puberty and menopause, osteoporosis, cosmetic appearance, and pregnancy.

Hormonal secretion that ultimately influences the menstrual cycle is regulated by a complex sequence of events involving the hypothalamic-pituitary axis in the brain and the ovaries. The first day of the menstrual cycle generally coincides with the onset of menses (normal menstrual bleeding) and is typically the day after spotting begins. This period is often also called the Menstrual Phase (days -3 to +3). Onset of menses is followed by the Follicular Phase (days 4 to 9), which is associated with a rise and then fall of estradiol. The next phase of the menstrual cycle is the Ovulatory Phase (days 10-17), is associated with ovulation, and peak levels of follicle stimulating hormone (FSH) and luteal hormone (LH). The final phase of the menstrual cycle is the Luteal Phase ( days -12 to ?4), characterized by rising levels of progesterone (which then fall if fertilization does not occur), and another rise and fall of estradiol. This phase is usually 14 days and is less variable than the Follicular Phase, which is often 10-17 days.

Some women experience Catamenial (Gr. Katamenios = monthly) seizures, meaning that seizures tend to cluster at various times of the menstrual cycle. Most commonly, seizures occur during menses, but can also occur during the ovulatory, follicular and luteal phases of the cycle. Explanations for seizures at these various times include the withdrawal of progesterone, along with an increased ratio of estrogen to progesterone, and inadequate luteal phases. Anti-seizure drug levels may also fluctuate throughout the cycle. Management strategies for women with Catamenial Epilepsy include first documenting and confirming that this is in fact the diagnosis, second considering treatment options depending on the cause. Treatment options include conventional anti-seizure medications, hormonal therapy, steroid therapy, and acetazolamide. Details about these treatment options, including which one is most appropriate and any possible adverse effects are best obtained in an appointment setting.

Though many women with epilepsy will not have clearly definable catamenial epilepsy, there are still several other relevant factors to consider with regard to reproductive health and sexual function. Menstrual factors include abnormally shortened or prolonged menstrual cycles and abnormal bleeding patterns. In addition, some women may have anovulatory cycles. It is not uncommon for women with previously "normal" (regular 24-35 day cycles) to find that the onset of their menses becomes unpredictable (occurring before day 24 or after day 35). Bleeding may also occur mid-cycle. Blood flow may become irregular or heavy, and duration may be prolonged. These abnormalities, in isolation or combination can be expected to occur in 1/3 of women with epilepsy.

Fertility is also a consideration in women with epilepsy. Fertility rates may be reduced by 1/3 or more. The most common explanations include anovulatory cycles, menstrual abnormalities, significant weight gain, and sex hormone alterations secondary to anti-seizure drug use. The anti-seizure medication most commonly linked to anovulatory cycles is valproic acid. This drug is associated with polycysitc ovary syndrome (PCOS), significant weight gain, and elevation of gonadal and adrenal androgens. PCOS is characterized by hirsutism (facial hair), obesity, acne, elevated androgen levels, elevated LH/FSH ratios, chronic anovulation, and insulin resistance. This syndrome is also associated with carbohydrate intolerance, hypercholesterolemia, and an increased risk for endometrial cancer. Other anti-seizure drugs may also be associated with alterations in steroid hormone levels, including carbamazepine, henobarbital, and phenytoin. Further information regarding fertility factors should be obtained directly from a physician team, including a neurologist who specializes in epilepsy and an obstetrician who specializes in fertility.

With regard to conception and contraception, as noted conception may prove difficult for some women with epilepsy. Preventing pregnancy while on anti-seizure medication may also be troublesome if adequate knowledge of the interaction between these drugs and oral contraceptive pills (OCP's) is lacking. Certain anti-seizure drugs may interfere with the function of OCP's by increasing their metabolism. Thus higher doses of OCP are required, or alternative contraceptive methods must be employed.

General health is also an issue for women with epilepsy taking anti-seizure medications. Since all anti-seizure medications are associated with a side effect profile, the way in which possible side effects might impact an individual's life require due consideration, along with other relevant factors (cost, seizure classification, blood monitoring, etc). Certain drugs can cause undesired cosmetic changes, such as weight gain, weight loss, hair loss, hair growth, tremulousness, facial acne, and gum enlargement, to name a few. In addition, certain anti-seizure drugs are known to impair Vitamin D absorption and to ultimately hasten reductions in bone density. This is an issue for patients who suffer frequent falls due to seizures or who are either post-menopause. A different anti-seizure medication may be required, or the patient may require supplements.

In all instances, the specific topic of women and epilepsy is complicated and merits special attention. The patient and her physician team should discuss the relevant factors as part of an informed decision-making process.